ABSTRACT: One needs to think outside of the box, as one of us (Ronald B Luftig) learned from many years as a mathematician, and a biophysicist.In this short Review, the need to focus on producing high levels of neutralizing antibodies (NAbs) to incoming and conformationally altered virus after it has bound to CD4+ cells is essential.Increasing the number of gp120 molecules on the surface of L-2 particles, could allow for an enhanced number of NAbs.The attempt at increasing CD8+ T cell responses in recent vaccine trials has not worked perhaps because it may have allowed HIV to enter into remote sanctuaries. Our approach focuses on increasing NAbs, before high levels of CD8+ T cells are produced.